The production of swine for food use is an important industry in the United States with more than 100 million pigs produced each year. There is demand among producers for agents that increase productivity and performance such as by increasing the proportion of meat per carcass, decreasing the amount of fat, decreasing the percent fat mass, increasing the feed efficiency, increasing average daily gain (ADG), decreasing feed-to-gain ratio (F:G), and modulation of meat quality.
The androgen receptor (“AR”) is a ligand-activated transcriptional regulatory protein that mediates induction of male sexual development and function through its activity with endogenous androgens. The androgenic hormones are steroids which are produced in the body by the testes and the cortex of the adrenal gland or can be synthesized in the laboratory. Androgenic steroids play an important role in many physiologic processes, including the development of muscle and bone mass. The endogenous steroidal androgens include testosterone and dihydrotestosterone (“DHT”). Other steroidal androgens include esters of testosterone, such as the cypionate, propionate, phenylpropionate, cyclopentylpropionate, isocarporate, enanthate, and decanoate esters, and other synthetic androgens such as 7-Methyl-Nortestosterone (“MENT’) and its acetate ester (Sundaram et al., “7 Alpha-Methyl-Nortestosterone (MENT).
Selective Androgen Receptor Modulators (SARMs) include nonsteroidal compounds which retain the anabolic activity of endogenous androgens with reduced androgenic activity (i.e., lesser effects in the prostate). SARMs beneficially promote muscle growth in humans and can treat, suppress, prevent, or inhibit muscle wasting.
The ability of a SARM to beneficially promote muscle growth in humans can be used as an alternative means to promote lean muscle deposition in animals, feedlot animals, beef cattle or finishing livestock.
Currently, Paylean® (Ractopamine hydrochloride) is the only commercially available feed additive to increase growth rates and lean efficiency in finishing swine. Ractopamine mediates its effect by stimulating β-adrenergic receptor.
β-adrenergic agonists are a class of chemical compounds that stimulates β-receptors in the autonomic nervous system. This stimulation of β-receptors has the effect is of promoting growth in animals when the β-agonists are fed to the animals.
Although β-agonists are effective in promoting the production of lean mass, there are three major drawbacks which limit the market for Paylean®. The most significant drawback to using β-agonists is the increased susceptibility to stress in treated animals resulting in increased injuries. Secondly, the European Union has banned β-agonists from use in food-producing animals since 1996. Finally, treatment with β-agonists results in rapid desensitization of the β-adrenergic receptors, thereby limiting the amount of time an animal can benefit from this treatment (typically <4 wks).
Accordingly, there is a need for methods in which new compounds may be used to improve carcass characteristics and increase lean mass gain in animals.